Calcium-Independent Activation of an Allosteric Network in Langerin by Heparin Oligosaccharides

Abstract

The C-type lectin receptor Langerin is a glycan-binding protein that serves as an uptake receptor on Langerhans cells and is essential for the formation of Birbeck granules. Whereas most Langerin ligands are recognized by a canonical Ca²⁺ -dependent binding site, heparins have been proposed to make additional contacts to a secondary, Ca²⁺ -independent site. Glycan array screening and biomolecular NMR spectroscopy were employed to investigate the molecular mechanism of these interactions. We observed that binding of heparin hexasaccharides to a secondary site did not require the presence of Ca²⁺ and activated a previously identified intradomain allosteric network of Langerin (thus far only associated with Ca²⁺ affinity and release). We propose a communication hub between these two binding sites, which sheds new light on modulatory functions of Langerin-heparin interactions.

Keywords: Birbeck granules; Langerin; allosterism; glycan-binding proteins; heparin; molecular recognition.